Abstract
Abstract Adjuvants enhance immune response to antigens and increase vaccine efficacy. We investigated the relative potency of adjuvants with diverse mechanism of action: a natural killer T cell activating ligand (alpha-galactosylcermide, αGalCer), a toll-like receptor 9 ligand (CpG B), a liposomal nanoparticle (R-DOTAP) and a plant saponin from Quillajira saponaria (QS21). We used OVA TCR transgenic model and also compared systemic vs mucosal routes of delivery for inducing antigen-specific CD8 T cell responses in naïve and syngeneic tumor-bearing mice. Wild type C57Bl/6 mice were vaccinated with OVA admixed with the adjuvants via subcutaneous (SC) or intranasal (IN) route 1d after adoptive transfer of the OT-I cells. Single cell suspensions of tissues 7d post-vaccination were analyzed using flow cytometry for OT-1 cells (CD45.1+Vα2+). Vaccination by either SC or IN route using QS21 adjuvant showed the most potent trafficking and activation of CD8+ T cells to both systemic and at mucosal sites, with the highest response observed in the lungs. Vaccination using the αGalCer by the IN route was relatively more effective than when delivered by the SC route, but the responses with αGalCer were lower compared to that with the QS21 adjuvant. However, vaccination of mice bearing B16F10-OVA resulted in preferential trafficking of OT-I cells to the tumors with much reduced numbers at the other tissues. Once again, these responses were robustly higher with QS21 vaccine delivered by either SC or IN route and the OT-1+ T cells from the tumors exhibited higher levels of functional and proliferating properties based on IFN-γ and Ki67 staining. Our results demonstrate that QS21 is a potent adjuvant for prophylactic as well as therapeutic vaccination applications.
Published Version
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